الفهرس 
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Abstract
The present study was performed on sixty cases of DLBCL and 11 cases of reactive follicular hyperplasia as a control group.
The age of selected lymphoma cases ranged between 12 and 82 years with a median of 53.5 years and a mean ± SD of 53.58 ±14.27. Thirty cases were males [50%] and 30 cases [50%] were females. All cases were presented as nodal lymphoma [100%] including 7 [11.7%] splenic, 7[11.7%] head and neck lymph nodes and 46 [76.6%] in other different sites with 23 [38.3%] cases presented by localized lymphadenopathy and 37[61.7%] cases presented by generalized lymphadenopathy.
Splenic involvement was detected in 19 cases [31.7%] while bone marrow involvement was detected in 31 cases [51.7%]. Of the studied cases, eleven cases [18.3%] showed evidence of relapse. Regarding LDH level, it ranged from198 to 1312 IU/L with a mean ± SD of 530.4 ± 275 and a median of 435 IU/L. Thirty five cases[58.3%] presented by high LDH level (≥500IU/L) . By using Ann-Arbor staging system, stage III predominated constituting 45% of cases [ 27/60] followed by stage IV (19 cases[ 31.7%]) then stage II (10[16.7%]) and finally stage I constituting only 16.7%[ 4 cases].
Regarding performance status, 50 cases [83.3%] had performance status ≤ 2 and 10 cases [16.7%] had performance status > 2.
Survival data were available for 44 cases only. Seven cases died of their disease in a period ranged between1-24 month and 37 cases still alive till the end of the study. Survival time in studied cases
ranged from 1 to 105 months with a mean ± SD of 16.25 ±17.8 and a median of 9.5 months.
Regarding revised international prognostic index {RIPI}, most of cases [78.3%] were of good RIPI and 21.7 % were of poor RIPI. With stratification of IPI according to age of patients [age adjusted IPI], intermediate risk predominated constituting 47.5% in patients lower than 60 years and 55% of cases above 60 years. Regarding response to therapy, data were available for 48 cases only where 36 [75%] cases of them showed complete response to therapy
Regarding histologic type, 32 cases [53.3%] were centroblastic type, 21 [35%] of cases were immunoblastic and 7 cases were of other types. Regarding molecular subtyping, 30 cases [50%] were germinal and 30 cases [50%] were non germinal type. The present study assessed stromal -1 signature using SPARC-1 and stromal-2 signature using CD31 expression in 60 cases of DLBCL, classified into germinal and non-germinal subtypes using Han’s algorithm. Regarding MVD reactive nodal hyperplasia cases showed significant low MVD in comparison to DLBCL cases [P=0.027], GCB cases [P=0.028] and non-GCB cases [P=0.028].
In DLBCL cases, MVD was significantly associated with splenic involvement [P=0.029] and high mitoses [P=0.045] and capsular invasion [P=0.035]. In non-germinal cases, high MVD was significantly associated with high mitoses [P=0.012] and splenic involvement [P=0.032] while in germinal cases, high MVD was negatively correlated with LDH level [P=0.045].
Regarding SPARC expression, reactive follicular hyperplasia cases showed significant low SPARC expression (90% cases) in comparison to GCB cases (10% of cases)[P=0.000] and in comparison to non-GCB cases (10% of cases)[P=0.000]
In DLBCL, extent of SPARC positivity was significantly correlated with splenic involvement [P=0.03]. In germinal cases, higher SPARC was positively correlated with generalized lymphadenopathy [P=0.044]. While in non-germinal cases, higher SPARC was positively correlated with localized lymphadenopathy [P=0.02] and splenic involvement [P=0.012].
Regarding combined stromal signature, 28 cases [46.7%] showed high SPARC and high MVD, 26 cases [43.3%] showed high SPARC and low MVD, 2 [3.3%] showed low SPARC and high MVD and 4 cases[ 6.7%] showed low SPARC and low MVD.
We applied biologic prognostic model in an attempt to simulate gene expression profile by immunohistochemistry using the results of cell of origin [germinal or non-], stromal -1 signature [SPARC and stromal – 2 signature [CD31].
We found that cases with high biologic prognostic score [2-3] showed statistical significant association with higher rate of splenic involvement [P=0.04]. Also, cases with low BPM score showed higher rate of complete response to therapy [23 case (63.9%)] in comparison to cases with high BPM [13 case (36.1%)] with a nearly statistical significance [P=0.08].
Regarding overall survival study, younger patient experienced shorter survival compared to older patients (P=0.02) and patients presented with poor performance status {PS>2} showed poorer
survival compared to patients associated with good performance status {PS≤2} [P=0.000]
By using Cox- regression, performance status was the only independent prognostic factor affecting patient’s overall survival [P=0.002]